Cultured human cells will be used to evaluate fundamental and practical aspects of treatment of human neoplasms with densely ionizing radiations. Human kidney (line T-1) cells cultured in vitro have been used for over a decade as a human cell survival model in high LET radiation biology. These will be exposed in the proposed research to heavy ions, negative pions, alpha particles, fast neutrons and gamma rays. Cell survival (colony-forming ability) will be the endpoint in experiments designed to explore fundamental aspects of high LET radiation action: the dependence of radiation sensitivity on the size and shape of the cell nucleus, the dependence of radiation effectiveness on charged particle velocity and charge, dose-response functions and oxygen dependence at very low doses. The effect of ploidy on mammalian cell radiosensitivity at high and low LET will be evaluated using cells of mammals with low chromosome number. Practical aspects of high LET radiotherapy will be investigated in dose fractionation experiments, synchronous cell experiments, and postirradiation life-cycle-analysis experiments in order to develop a better understanding of time-dose relationships.